Assessment of Candidate Loci in Neurological diseases

在过去的一段时间里，我们研究了各种神经系统疾病中的PRKN，PINK，APP，PS1，PS2，PRNP，PGRN和ATXN 2/3突变。我们继续我们的工作，在脊髓小脑共济失调，通过建立频率的SCA 15突变，我们确定了一个大的队列，并通过后续的尚未发表的SCA基因座，我们确定了使用同源性作图。此外，我们继续与NINDS和NHGRI的合作者合作，以确定哪些患者具有LRRK 2突变，并可以在这些患者及其尚未受影响的家庭成员前瞻性地参与我们的合作研究。 此外，今年我们对帕金森病的APOE变异性进行了评估，因为以前所有的研究都提供了一些不明确的结果。这项工作涉及在一个非常大的PD患者队列中分析APOE的常见编码变体（APOE类型）（这项工作目前正在审查中）。 我们还进行了评估的候选基因座隐性共济失调在一系列患者从突尼斯谁有共济失调。这项工作使我们能够将这些家庭解析为具有已知突变的家庭，以及那些应该优先进行进一步遗传工作以寻找新的疾病遗传原因的家庭。

In the last period we have worked on PRKN, PINK, APP, PS1, PS2, PRNP, PGRN and ATXN2/3 mutations in varied neurological diseases. We have continued our work in spinocerebellar ataxias by establishing the frequency of SCA15 mutations identified by us in a large cohort and by follow up of as yet unpublished SCA loci identified by us using autozygosity mapping. In addition we continue to work with our collaborators at NINDS and NHGRI to establish which of our patients have LRRK2 mutations and can be enrolled in our collaborative study following these patients and their as yet unaffected family members prospectively. In addition this year we have performed an assessment of APOE variability in Parkinson's disease, as all previous studies provided somewhat unclear results. This work involved analysis of the common coding variants (epsilon types) in APOE in a very large cohort of PD patients (this work is currently under review). We have also performed an assessment of candidate loci for recessive ataxia in a series of patients from Tunisia who have ataxia. This work allows us to parse such families into those with known mutations, and those that should be prioritized for further genetic work aimed at finding new genetic causes of disease.